tbuckley/cabot-search huggingface dataset:
Clinical significance of clonal hematopoiesis in the setting of autologous stem cell transplantation for lymphoma
Authors: Tracy Lackraj, Sharon Ben Barouch, Jessie J. F. Medeiros, Stephanie Pedersen, Arnavaz Danesh, Mehran Bakhtiari, Michael Hong, Kit Tong, Jesse Joynt, Andrea Arruda, Mark D. Minden, John Kuruvilla, Sita Bhella, Vishal Kukreti, Michael Crump, Anca Prica, Christine Chen, Yangqing Deng, Wei Xu, Trevor J. Pugh, Armand Keating, John E. Dick, Sagi Abelson, Robert Kridel
Journal: American Journal of Hematology (2022)

Abstract Autologous stem cell transplantation (ASCT) remains a key therapeutic strategy for treating patients with relapsed or refractory non‐Hodgkin and Hodgkin lymphoma. Clonal hematopoiesis (CH) has been proposed as a major contributor not only to the development of therapy‐related myeloid neoplasms but also to inferior overall survival (OS) in patients who had undergone ASCT. Herein, we aimed to investigate the prognostic implications of CH after ASCT in a cohort of 420 lymphoma patients using ultra‐deep, highly sensitive error‐correction sequencing. CH was identified in the stem cell product samples of 181 patients (43.1%) and was most common in those with T‐cell lymphoma (72.2%). The presence of CH was associated with a longer time to neutrophil and platelet recovery. Moreover, patients with evidence of CH had inferior 5‐year OS from the time of first relapse (39.4% vs. 45.8%, p = .043) and from the time of ASCT (51.8% vs. 59.3%, p = .018). The adverse prognostic impact of CH was not due to therapy‐related myeloid neoplasms, the incidence of which was low in our cohort (10‐year cumulative incidence of 3.3% vs. 3.0% in those with and without CH, p = .445). In terms of specific‐gene mutations, adverse OS was mostly associated with PPM1D mutations (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.13–2.67, p = .011). In summary, we found that CH is associated with an increased risk of non‐lymphoma‐related death after ASCT, which suggests that lymphoma survivors with CH may need intensified surveillance strategies to prevent and treat late complications.
Citius, Altius, Fortius
Authors: Bruce B. Dan
Journal: JAMA (1984)

In recognition of the first summer Olympic Games held in the United States in more than 50 years, we are dedicating this issue ofThe Journalto the topic of sports medicine. We initiated our own competition by inviting authors to submit manuscripts on exercise physiology, training, nutrition, or any subject relevant to the aspirations typified by the Olympic Games. We received more than 100 major contributions for this singular issue. After undergoing rigorous review, the articles presented herein represent those selected by the editors for our Olympic issue. Sports medicine, a relatively new specialty, owes its emergence to the technological advances of modern society and the burgeoning of leisure-time activity. Our ancestors, the hunters and gatherers of a more primitive planet, depended on their physical talents for existence. They survived each day on their ability to find dinner while avoiding becoming something else's lunch. The fleet of foot found
Rituximab in Newly Diagnosed Generalized Myasthenia Gravis
Authors: Miguel Chuquilin, Richard Barohn
Journal: JAMA Neurology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Holding Pharmaceutical and Medical Device Executives Accountable as Responsible Corporate Officers
Authors: C. Joseph Ross Daval, Jerry Avorn, Aaron S. Kesselheim
Journal: JAMA Internal Medicine (2022)

When a drug or medical device company violates federal law, the government has a powerful tool to use: the Park doctrine. The aim of the doctrine is to protect patients from the harms of an unsafe or fraudulent medical marketplace by targeting the executives who run the companies that make revenues on these products while violating federal law, rather than have that risk borne by patients or impersonal corporate entities; however, public reports of drug and device company executives being prosecuted in Park doctrine cases are uncommon.To identify Park prosecutions and characterize their role in US Department of Justice (DOJ) enforcement efforts related to misconduct in the drug and medical device industry.A systematic search of Westlaw, Google Scholar, DOJ press releases, and the legal literature was conducted.Thirteen cases of executives from 6 drug and medical device companies prosecuted under the Park doctrine since 2000 were identified. The prosecutions resulted in 11 guilty pleas and 2 jury trials, leading to 2 convictions. Of the 6 companies, 3 were drug manufacturers, 2 were medical device manufacturers, and 1 was a compounding pharmacy. All 3 drug manufacturers were opioid manufacturers, of which 2 executives were charged for unlawful promotion, and 1 was charged for manufacturing errors. Both device manufacturer executives were charged with unlawful promotion. All but 3 prosecutions alleged the defendants' complicity or personal involvement in the misconduct, which Park does not require. By contrast, most large settlements with the DOJ over alleged misconduct in the past 2 decades did not result in individual liability for executives.These findings suggest that the government has not exercised the full scope of its authority to prosecute corporate officials responsible for the illegal behavior of the drug and device companies they run. Enforcement under a reinvigorated Park doctrine could better promote the doctrine's goal of protecting patients.
Antenatal Steroid Exposure Among Term Newborns
Authors: Taylor S. Freret, Kaitlyn E. James, Alexander Melamed, Cynthia Gyamfi-Bannerman, Anjali J. Kaimal, Mark A. Clapp
Journal: JAMA Pediatrics (2022)

This cross-sectional study evaluates the association between dissemination of the Antenatal Late Preterm Steroid trial and changes in steroid exposure among term newborns.
Perioperative Gabapentin Use in Older Adults
Authors: Tasce Bongiovanni, Timothy S. Anderson, Zachary A. Marcum
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Human Papillomavirus Vaccination Before and During the COVID-19 Pandemic
Authors: Jenny K. R. Francis, Sitara M. Weerakoon, Serena L. Lucas, Matthew S. Mathew, Julia C. Durante, Nancy Kelly, Jasmin A. Tiro
Journal: JAMA Network Open (2022)

This cross-sectional study compares human papillomavirus vaccinations by age and season before and during the COVID-19 pandemic.
Association of Simultaneous vs Delayed Resection of Liver Metastasis With Complications and Survival Among Adults With Colorectal Cancer
Authors: Yibin Wu, Anrong Mao, Huipeng Wang, Guojiu Fang, Jiamin Zhou, Xigan He, Sanjun Cai, Lu Wang
Journal: JAMA Network Open (2022)

Importance Simultaneous or delayed resection of synchronous liver metastasis (SLM) with primary colorectal cancer (CRC) remains a controversial topic. Objective To investigate the outcomes of simultaneous vs delayed resection in patients with resectable SLM. Design, Setting, and Participants This comparative effectiveness research study included 1569 patients with resectable SLM who underwent curative-intent liver resection at 3 independent centers in China between January 1, 2000, to December 31, 2019. A 1:1 propensity score matching was performed. Follow-up was completed on August 31, 2021, and the data were analyzed from April 1 to 30, 2022. Main Outcomes and Measures Primary outcome was the percentage of patients with at least 1 major complication within 60 days after surgery. Secondary outcomes were intraoperative and postoperative complications, overall survival (OS), and cancer-specific survival (CSS) rates. Results Among the 1569 patients included, 1057 (67.4%) underwent delayed resection (719 men [68.0%] with a mean [SD] age of 57.4 [11.2] years), and 512 patients (310 men [60.5%] with a mean [SD] age of 57.1 [10.5] years) underwent simultaneous resection. Matching yielded 495 pairs of patients underwent simultaneous resection. The percentage of major perioperative complications did not differ between the simultaneous and delayed resection groups (34.1% vs 30.0%; P = .89). The OS rates were 65.2% at 3 years, 47.1% at 5 years, and 38.0% at 8 years for the delayed resection group and 78.0% at 3 years, 65.4% at 5 years, and 63.1% at 8 years for the simultaneous resection group (hazard ratio [HR], 1.42; 95% CI, 1.10-1.85, P = .003). The CSS rates were 68.3% at 3 years, 48.5% at 5 years, and 37.1% at 8 years for the delayed resection group and 79.2% at 3 years, 67.2% at 5 years, and 65.9% at 8 years for the simultaneous resection group (HR, 1.45; 95% CI, 1.14-1.98; P = .004). On subgroup analysis comparing the 2 strategies according to the KRAS sequence variation status, the OS rates (HR, 1.61; 95% CI, 1.45-2.18; P &amp;lt; .001) and CSS rates (HR, 1.62; 95 CI, 1.40-1.87; P = .003]) in the simultaneous resection group were significantly better than those in the delayed resection group in patients with KRAS wild-type tumors. Conclusions and Relevance Results of this study suggest that complication rates did not differ when CRC and SLM were resected simultaneously and that the survival benefits of simultaneous resection were restricted to patients with KRAS wild-type tumors. Integrating molecular features into the treatment decision is a basis for accurate, individualized treatments.
Accountability of Health Care Executives for Illegal Activities of Pharmaceutical and Medical Device Companies
Authors: Jacob T. Elberg
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Validation of the PEN-FAST Score in a Pediatric Population
Authors: Ana Maria Copaescu, Sara Vogrin, Greg Shand, Moshe Ben-Shoshan, Jason A. Trubiano
Journal: JAMA Network Open (2022)

This cohort study examines a clinical decision model for penicillin allergies among pediatric patients; the model considers when reactions occurred; whether patients experienced angioedema, anaphylaxis, or a severe cutaneous adverse reaction; and whether treatment was required.
Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity
Authors: Wissam Ghusn, Alan De la Rosa, Daniel Sacoto, Lizeth Cifuentes, Alejandro Campos, Fauzi Feris, Maria Daniela Hurtado, Andres Acosta
Journal: JAMA Network Open (2022)

Importance No retrospective cohort study has assessed the effectiveness of semaglutide at doses used in randomized clinical trials to treat obesity (ie, 1.7 and 2.4 mg). Objective To study weight loss outcomes associated with semaglutide treatment at doses used in randomized clinical trials for patients with overweight or obesity. Design, Setting, and Participants This cohort study, conducted at a referral center for weight management, retrospectively collected data on the use of semaglutide for adults with overweight or obesity between January 1, 2021, and March 15, 2022, with a follow-up of up to 6 months. A total of 408 patients with a body mass index (BMI) of 27 or more were prescribed weekly semaglutide subcutaneous injections for 3 months or more. Patients with a history of bariatric procedures, taking other antiobesity medications, and with an active malignant neoplasm were excluded. Exposures Weekly 1.7-mg or 2.4-mg semaglutide subcutaneous injections for 3 to 6 months. Main Outcomes and Measures The primary end point was the percentage of weight loss. Secondary end points were the proportion of patients achieving weight loss of 5% or more, 10% or more, 15% or more, and 20% or more after 3 and 6 months and the percentage of weight loss for patients with or without type 2 diabetes after 3 and 6 months. Results The study included 175 patients (132 women [75.4%]; mean [SD] age, 49.3 [12.5] years; mean [SD] BMI, 41.3 [9.1]) in the analysis at 3 months and 102 patients at 6 months. The mean (SD) weight loss after 3 months was 6.7 (4.4) kg, equivalent to a mean (SD) weight loss of 5.9% (3.7%) ( P &amp;lt; .001), and the mean (SD) weight loss after 6 months was 12.3 (6.6) kg, equivalent to a mean (SD) weight loss of 10.9% (5.8%) ( P &amp;lt; .001 from baseline). Of the 102 patients who were followed up at 6 months, 89 (87.3%) achieved weight loss of 5% or more, 56 (54.9%) achieved weight loss of 10% or more, 24 (23.5%) achieved weight loss of 15% or more, and 8 (7.8%) achieved weight loss of 20% or more. Patients with type 2 diabetes had a lower mean (SD) percentage weight loss at 3 and 6 months compared with those without type 2 diabetes: 3.9% (3.1%) vs 6.3% (3.7%) at 3 months ( P = .001) and 7.2% (6.3%) vs 11.8% (5.3%) at 6 months ( P = .005). Conclusions and Relevance The results of this cohort study suggest that weekly 1.7-mg and 2.4-mg doses of semaglutide were associated with weight loss similar to that seen in randomized clinical trials. Studies with longer periods of follow-up are needed to evaluate prolonged weight loss outcomes.
The evolutionary dynamics of extrachromosomal DNA in human cancers
Authors: Joshua T. Lange, John C. Rose, Celine Y. Chen, Yuriy Pichugin, Liangqi Xie, Jun Tang, King L. Hung, Kathryn E. Yost, Quanming Shi, Marcella L. Erb, Utkrisht Rajkumar, Sihan Wu, Sabine Taschner-Mandl, Marie Bernkopf, Charles Swanton, Zhe Liu, Weini Huang, Howard Y. Chang, Vineet Bafna, Anton G. Henssen, Benjamin Werner, Paul S. Mischel
Journal: Nature Genetics (2022)

Abstract Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumor growth, drug resistance and shorter survival. Currently, the impact of nonchromosomal oncogene inheritance—random identity by descent—is poorly understood. Also unclear is the impact of ecDNA on somatic variation and selection. Here integrating theoretical models of random segregation, unbiased image analysis, CRISPR-based ecDNA tagging with live-cell imaging and CRISPR-C, we demonstrate that random ecDNA inheritance results in extensive intratumoral ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted treatment. Observed ecDNAs benefit host cell survival or growth and can change within a single cell cycle. ecDNA inheritance can predict, a priori, some of the aggressive features of ecDNA-containing cancers. These properties are facilitated by the ability of ecDNA to rapidly adapt genomes in a way that is not possible through chromosomal oncogene amplification. These results show how the nonchromosomal random inheritance pattern of ecDNA contributes to poor outcomes for patients with cancer.
MRI techniques for immunotherapy monitoring
Authors: Doreen Lau, Pippa G Corrie, Ferdia A Gallagher
Journal: Journal for ImmunoTherapy of Cancer (2022)

MRI is a widely available clinical tool for cancer diagnosis and treatment monitoring. MRI provides excellent soft tissue imaging, using a wide range of contrast mechanisms, and can non-invasively detect tissue metabolites. These approaches can be used to distinguish cancer from normal tissues, to stratify tumor aggressiveness, and to identify changes within both the tumor and its microenvironment in response to therapy. In this review, the role of MRI in immunotherapy monitoring will be discussed and how it could be utilized in the future to address some of the unique clinical questions that arise from immunotherapy. For example, MRI could play a role in identifying pseudoprogression, mixed response, T cell infiltration, cell tracking, and some of the characteristic immune-related adverse events associated with these agents. The factors to be considered when developing MRI imaging biomarkers for immunotherapy will be reviewed. Finally, the advantages and limitations of each approach will be discussed, as well as the challenges for future clinical translation into routine clinical care. Given the increasing use of immunotherapy in a wide range of cancers and the ability of MRI to detect the microstructural and functional changes associated with successful response to immunotherapy, the technique has great potential for more widespread and routine use in the future for these applications.
Adipocyte IRE1α promotes PGC1α mRNA decay and restrains adaptive thermogenesis
Authors: Yong Chen, Zhuyin Wu, Shijia Huang, Xiaoxia Wang, Sijia He, Lin Liu, Yurong Hu, Li Chen, Peng Chen, Songzi Liu, Shengqi He, Bo Shan, Ling Zheng, Sheng-Zhong Duan, Zhiyin Song, Lei Jiang, Qiong A. Wang, Zhenji Gan, Bao-Liang Song, Jianmiao Liu, Liangyou Rui, Mengle Shao, Yong Liu
Journal: Nature Metabolism (2022)
Implementing precision medicine in a regionally organized healthcare system in Sweden
Authors: Thoas Fioretos, Valtteri Wirta, Lucia Cavelier, Eva Berglund, Mikaela Friedman, Michael Akhras, Johan Botling, Hans Ehrencrona, Lars Engstrand, Gisela Helenius, Therese Fagerqvist, David Gisselsson, Sofia Gruvberger-Saal, Ulf Gyllensten, Markus Heidenblad, Kina Höglund, Bo Jacobsson, Maria Johansson, Åsa Johansson, Maria Johansson Soller, Maréne Landström, Pär Larsson, Lars-Åke Levin, Anna Lindstrand, Lovisa Lovmar, Anna Lyander, Malin Melin, Ann Nordgren, Gunnel Nordmark, Paula Mölling, Lars Palmqvist, Richard Palmqvist, Dirk Repsilber, Per Sikora, Bianca Stenmark, Peter Söderkvist, Henrik Stranneheim, Tobias Strid, Craig E. Wheelock, Mia Wadelius, Anna Wedell, Anders Edsjö, Richard Rosenquist
Journal: Nature Medicine (2022)
Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity
Authors: Wenming Huang, Chun Kew, Stephanie de Alcantara Fernandes, Anna Löhrke, Lynn Han, Constantinos Demetriades, Adam Antebi
Journal: Nature Aging (2022)

Changes in splicing fidelity are associated with loss of homeostasis and aging, yet only a handful of splicing factors have been shown to be causally required to promote longevity, and the underlying mechanisms and downstream targets in these paradigms remain elusive. Surprisingly, we found a hypomorphic mutation within ribonucleoprotein RNP-6/poly(U)-binding factor 60 kDa (PUF60), a spliceosome component promoting weak 3'-splice site recognition, which causes aberrant splicing, elevates stress responses and enhances longevity in Caenorhabditis elegans. Through genetic suppressor screens, we identify a gain-of-function mutation within rbm-39, an RNP-6-interacting splicing factor, which increases nuclear speckle formation, alleviates splicing defects and curtails longevity caused by rnp-6 mutation. By leveraging the splicing changes induced by RNP-6/RBM-39 activities, we uncover intron retention in egl-8/phospholipase C β4 (PLCB4) as a key splicing target prolonging life. Genetic and biochemical evidence show that neuronal RNP-6/EGL-8 downregulates mammalian target of rapamycin complex 1 (mTORC1) signaling to control organismal lifespan. In mammalian cells, PUF60 downregulation also potently and specifically inhibits mTORC1 signaling. Altogether, our results reveal that splicing fidelity modulates lifespan through mTOR signaling.
Monkeypox in a Young Infant — Florida, 2022
Authors: Katharine E. Saunders, Andrea N. Van Horn, Helen K. Medlin, Ann Carpenter, Philip A. Lee, Liliana Gutierrez, Joshua Dillon, Alexandra P. Newman, Anne Kimball, David W. McCormick, Danielle R. Stanek
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

In August 2022, the Florida Department of Health (FDOH) was notified of a suspected case of monkeypox in an infant aged <2 months who was admitted to a Florida hospital with a rash and cellulitis. This case report highlights findings from the related epidemiologic investigation and describes the public health actions taken. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.* This is the youngest patient with confirmed monkeypox infection in Florida to date.